7. Molecular modelling
analysis of epigallocatechin-3-gallate
Fazlul Huq
Discipline of Biomedical Science, School of Medical Sciences,
Faculty of Medicine, Cumberland Campus, C42, The University of
Sydney,
Lidcombe, NSW, Australia.
Phone: +61 2 9351 9522; Fax: +61 2 9351 9520 Email:
F.Huq@usyd.edu.au
Abstract
The major green tea
catechin (-)-epigallocatechin-3-gallate (EGCG) is a powerful
antioxidant with potent anti-inflammatory, apoptotic and cancer
preventive properties. Molecular modelling analyses based on
molecular mechanics, semi-empirical (PM3) and DFT (at B3LYP/6-31G*
level) calculations show that EGCG and its metabolites have large
LUMO-HOMO energy differences ranging from 4.5 to 5.9 eV, indicating
that the compounds would be moderate to highly inert kinetically.
The molecular surfaces of the compounds are found to abound in
neutral green and electron-rich red and yellow regions so that they
may be subject to lyophilic and electrophilic attacks. The abundance
of electron-rich regions on the molecular surfaces can explain why
EGCG and its metabolites would act as powerful antioxidants, thus
providing an explanation for their anticarcinogenic and other
propetctive roles. The molecular surfaces of EGCG and its
metabolites are also found to possess a small amount of
electron-deficient blue regions so that the compounds may be subject
to nucleophilic attacks. Nucleophilic attacks may be due to
glutathione and nucleobases in DNA as a result of which depletion of
glutathione and oxidation of nucleobases in DNA may occur. The
former would induce oxidative stress and hence cellular toxicity
whereas the latter would cause DNA damage. However, because of
kinetic inertness of the molecules and paucity of electron-deficient
regions, the rates of such adverse reactions are expected to be low.
Key words: Green
tea, epigallocatechin-3-gallate, antiatherogenic, antioxidant,
anticarcinogenic, molecular modelling
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